The specific aims of this proposal are to examine sequentially cell surface markers, surface ultrastructure and terminal deoxynucleotidyl transferase activity in blood and bone marrow lymphoid cells from children with acute lymphoblastic leukemia; to isolate and define subgroup populations of blood and bone marrow cells which contain terminal transferase employing cell separation studies; and to determine the relationship of these biochemical and biologic markers to disease activity, clinical course, prognosis and chemotherapeutic regimes. Terminal deoxynucleotidyl transferase is present normally only in high concentration in the thymus and in low concentration in the bone marrow. The enzyme has been found in the peripheral blood of acute lymphoblastic leukemia patients and in lymphoblastoid cell lines. Crude extracts of lymphoid cells from peripheral blood and bone marrow are assayed directly utililizing H3-dGTP as substrate and oligo d(pA)50 as initiator. The limit of sensitivity of the assay is 0.05 units per 10 to the 8th power cells. Spontaneous rosette formation with sheep erythrocytes will serve as a T cell marker. Rosette formation with complement coated sheep erythrocytes and determination of surface bound immunoglobulins using fluorescein conjugated anti IgT, IgM and IgA will be utilized as B cell markers. Surface morphology will be characterized using scanning electron microscopy following critical point preparation. Serial observations of terminal transferase activity, cell surface markers and surface morphology in a large group of patients with actute lymphoblastic leukemia may provide information which will have important implications for the classification, prognosis and therapy of this disease.